1. Field of the Invention
The present invention relates to aldol condensation reactions, and more specifically, to ionic liquid media for carrying out these reactions.
2. Description of the Related Art
Aldol condensation reactions, or aldolization reactions, are known in the art. See U.S. Pat. No. 6,090,986 to Godwin et al., incorporated by reference herein. Currently aldol reactions are carried out in aqueous solutions, which leads to the production of large quantities of wastewater. This wastewater is detrimental to the environment and cannot be treated or recycled for other uses in a cost-effective manner.
Aldol condensation reactions are also typically accompanied by side reactions that significantly reduce the yield of desired products. The result is that the unwanted products of these side reactions must be separated from the desired products and discarded as waste.
Two types of aldol condensation reactions frequently encountered are the self-aldol condensation (Aldol I) and cross-aldol condensation (Aldol II) reactions. In an Aldol I reaction, two molecules of the same aldehyde starting material react to form a reaction product. Alternatively, in an Aldol II reaction, two different aldehyde starting materials react to form a reaction product. In practice, the condensation of two molecules of the same aldehyde (Aldol I) to form an aldol is usually followed immediately by dehydration to form an unsaturated aldehyde with twice the original number of carbon atoms. In a Aldol II reaction, however, the condensation of two molecules of different aldehydes forms an aldol and, upon dehydration, further forms an unsaturated aldehyde having the sum of the carbon atoms of the two different aldehydes. Both Aldol I and Aldol II reactions are well known in the art, as are the conditions required to effect their condensation.
An important example of Aldol I is the condensation of n-butyraldehyde to form, following a hydrogenation step, 2-ethyl-hexanol, known in the art as a Guerbet alcohol.
U.S. Pat. No. 6,090,986 to Godwin et al. discloses an important example of Aldol II in the formation of 2,4-dimethyl-2-heptenal from condensing 2-methyl-pentanal and propanal. Following the aldol condensation step, the 2,4-dimethyl-2-heptenal product is preferably hydrogenated to produce the saturated aldehyde 2,4-dimethyl-heptanal, which can be further hydrogenated to form the alcohol 2,4-dimethyl heptanol or, alternatively, can be oxidized to form 2,4-dimethyl heptanoic acid. The final alcohol and acid products are in demand commercially.
The Aldol II reaction is often run by reacting formaldehyde and a second aldehyde starting material in a basic catalyst through several steps, including several aldol addition steps and a final crossed Cannizzaro reaction step, to form a neopolyol product. By definition, neopolyols are alcohols having two or more primary alcohol functional groups (CH2OH) plus a tetra-substituted carbon atom. The most commercially desired neopolyol products are pentaerythritol, trimethylol ethane, trimethylol propane, and neopentyl glycol, which are derived from reacting formaldehyde with the second aldehyde starting materials acetaldehyde, propionaldehyde, n-butyraldehyde and isobutyraldehyde, respectively. The formation of neopolyols is disclosed in more detail in Encyclopedia of Chemical Technology, Kirk-Othmer, Fourth Edition, Vol. 1, pp. 913-925 (John Wiley and Sons 1991), incorporated by reference herein. The structural formulae for the preferred 
neopolyols are as follows:
Unfortunately, each type of aldol condensation reaction results in the formation of unwanted side products. Hence, there is a need in the art for a method to increase the yield of desired aldol condensation products, while decreasing the amount of side reactions, in an efficient and cost-effective manner. There is also a need for a method to reduce the amount of wastewater produced from present aldehyde condensation reactions.
Ionic liquids are known in the art for use as solvents in various chemical reactions. See U.S. Pat. Nos. 5,824,832 and 5,731,101 both to Sherif et al., and PCT International Patent Publication Nos. WO 00/15594 and WO 00/32572, all incorporated herein by reference. An ionic liquid is a liquid that is composed entirely of ions. They are typically molten at low temperatures and are suitable for use as a catalyst and as a solvent in alkylation and polymerization reactions, as well as in dimerization, oligomerization, acetylation, metatheses, hydrogenation, hydroformylation, and copolymerization reactions.
A class of ionic liquids which is of special interest is the class of salt compositions which are salts with melting points below 100xc2x0 C. Such compositions are mixtures of components which are liquid at temperatures below the individual melting points of the components.
The application of ionic liquids to aldol condensation reactions has heretofore not been disclosed in the art. One reason is because not all ionic liquids will produce advantageous results when used as the reaction medium or catalyst for such reactions.
The present invention relates to a process for forming aldol condensation products which comprises reacting at least one aldehyde starting material in the presence of a neutral ionic liquid medium, which is stable towards air and water, and a basic catalyst. In a preferred embodiment, the ionic liquid is comprised of an imidazolium- or pyridinium-based cation and a BF4xe2x88x92 or PF6xe2x88x92 anion. The preferred aldehyde starting materials are typically formaldehyde, acetaldehyde, propionaldehyde, n-butyraldehyde and isobutyraldehyde, and mixtures of formaldehyde and one of the foregoing, although other aldehydes are also suitable. The use of an ionic liquid can provide for more convenient separation of the aldol product and/or recycling of the neutral ionic liquid medium.
In another embodiment, the instant invention comprises reacting at least one aldehyde starting material in the presence of a basic ionic liquid medium to form aldol condensation products. The preferred embodiment, in this case, is an ionic liquid that is rendered intrinsically basic by the presence of a hydroxyl group as an anionic species.
In a further embodiment, the present invention relates to a process for producing cross-aldol condensation products by reacting formaldehyde and a second aldehyde starting material in the presence of a neutral ionic liquid medium and basic catalyst. The condensation products are optionally, but preferably, further reacted to form neopolyol products. The preferred second aldehyde starting materials in this situation are acetaldehyde, propionaldehyde, n-butyraldehyde and isobutyraldehyde, while the resulting neopolyol products derived therefrom are pentaerythritol, trimethylol ethane, trimethylol propane, and neopentyl glycol, respectively.
In a similar vein, the just-described formation of neopolyol products may be accomplished by reacting formaldehyde with a second aldehyde starting material in a basic ionic liquid medium to produce the same condensation products and the eventual neopolyol products.
The phrase xe2x80x9caldol condensation xe2x80x9d or xe2x80x9caldolization xe2x80x9d is used herein to refer to the process whereby at least 2 aldehyde starting materials are reacted and, upon immediate dehydration, form aldol condensation products. Aldol I and Aldol II are the terms used to label two types of aldol condensation.
The term xe2x80x9cbase xe2x80x9d or xe2x80x9cbasic xe2x80x9d when used with xe2x80x9ccatalyst xe2x80x9d or xe2x80x9cionic liquid xe2x80x9d refers to Brxc3x8nsted bases having the ability to react with (neutralize) acids to form salts. The pH range of bases is from 7.1 to 14.
The word xe2x80x9cneutral xe2x80x9d refers to compounds having a pH of 7 under the Brxc3x8nsted acid-base theory.
The term xe2x80x9cneutral ionic liquid xe2x80x9d refers to ionic liquids with a molar fraction of (x=0.5) and exhibits neither Brxc3x8onsted nor Lewis acidity. This definition is derived from the fact that Lewis acidity can be expressed by the molar fraction (x). Conventionally, when (x=0.5) the mixture is labeled neutral, when (x greater than 0.5) the mixture is labeled acidic, and when (x less than 0.5) the mixture is labeled basic. For a more detailed explanation of the definition of neutral ionic liquids, see PCT International Patent Publication No. WO 00/15594.
The term xe2x80x9ccatalyst xe2x80x9d is used herein to include all forms of catalysis, including classic initiators, co-initiators, co-catalysts, activating techniques, etc.
The term xe2x80x9cneopolyol xe2x80x9d refers to an alcohol having two or more primary alcohol functional groups (CH2OH) plus a tetra-substituted carbon atom.
The present invention describes a new method to carry out aldol condensation reactions. By utilizing ionic liquids as reaction medium and/or catalyst it is possible to achieve higher selectivity for aldol condensation products. The investigated ionic systems are salts that have melting points below 100xc2x0 C. and can be utilized as liquid solvent media or catalysts for a wide variety of chemical processes. Unlike conventional solvent systems, these liquids exhibit low vapor pressure, tunable polarity, and high thermal stability. Depending on the choice of the ionic fragments, a reaction environment can be designed to accommodate the catalysis and the separation of a chemical process in the most efficient way. By combining base catalysis with the advantages of ionic liquids, it is possible to prepare aldol condensation catalyst media which exhibit the significant advantages of selectivity and recyclability over existing catalyst systems.
The ionic liquids used in this invention may be characterized by the general formula A+Bxe2x88x92, where A+ is a cationic species and Bxe2x88x92 is an anionic species. The preferred ionic liquid has organic cationic species and inorganic anionic species. The composition A+Bxe2x88x92 may be referred to herein as an ionic liquid moiety.
In one embodiment, this invention utilizes a neutral ionic liquid and a basic catalyst to form aldol condensation products. Preferred basic catalysts are the alkali metal hydroxides and alkali earth metal hydroxides. Most preferably, the basic catalyst is either sodium hydroxide or potassium hydroxide.
While the preparation of the neutral ionic liquids disclosed herein are accomplished using methods known to one skilled the art (see, e.g., U.S. Pat. No. 5,731,101, incorporated by reference herein, and PCT International Patent Publication No. WO 95/21871), a brief summary of their precursor cationic and anionic species follows. Many unsubstituted or substituted heterocyclic ring systems may be converted into a stable cation A+ through the process of alkylation, protonation, acylation or another method known to those skilled in the art (see, e.g., T. L. Gilchrist, xe2x80x9cHeterocyclic Chemistry xe2x80x9d (Wiley and Sons 1995)). Thus, precursors for A+ may be selected from, for example, imidazoles, pyridines, pyrazoles, thiazoles, isothiazoles, azathiozoles, oxothiazoles, oxazines, oxazolines, oxazoboroles, dithiozoles, triazoles, selenozoles, oxaphospholes, pyrroles, boroles, furans, thiophenes, phospholes, pentazoles, indoles, indolines, oxazoles, isooxazoles, isotriazoles, tetrazoles, benzofurans, dibenzofurans, benzothiophenes, dibenzothiophenes, thiadiazoles, pyrimidines, pyrazines, pyridazines, piperazines, piperidines, morpholenes, pyrans, annolines, phthalzines, quinazolines, quinoxalines, quinolines, isoquinolines, thazines, oxazines, and azaannulenes. In addition, acyclic organic systems are also suitable. Examples include, but are not limited to, amines (including amidines, imines, and guanidines), phosphines (including phosphinimines), arsines, stibines, ethers, thioethers, selenoethers and mixtures of the above.
From the above list, the preferred cationic species of the neutral ionic liquid used herein are either pyridinium- or imidazolium-based. The most preferred cationic species are 1-butyl-3-methyl imidazolium, 1-butyl-2,3-dimethyl imidazolium and 1-butyl-pyridinium. The chemical structures for the three preferred cationic species are drawn as follows: 
The precursors for the anionic species Bxe2x88x92 include, for example, salts, alkylates and halogenated salts of the Group IB, IIIA, IVA, VA, VIA, and VIIA elements of the periodic table, including borates, phosphates, nitrates, sulfates, triflates, halogenated copperates, antimonates, phosphates, phosphites, substituted and unsubstituted carboranes, poly-oxo metallates, substituted (fluorinated, alkylated, and arylated) and unsubstituted metalloboranes, substituted and unsubstituted carboxylates and triflates, and mixtures thereof. The periodic table used herein to reference the above-identified groups of elements is from Hawley""s Condensed Chemical Dictionary, Thirteenth Edition, Richard J. Lewis, Sr., inside front cover (John Wiley and Sons, Inc. 1997). The anion Bxe2x88x92 may also be a non-coordinating anion such as tetra[pentafluoro phenyl] borane. Examples of some of the above include BF4xe2x88x92, PF6xe2x88x92, CF3SO3xe2x88x92, CF3COOxe2x88x92, SbF6xe2x88x92, [CuCl2]xe2x88x92, AsF6xe2x88x92, SO4xe2x88x92, CF3CH2CH2COOxe2x88x92, (CF3SO2)3Cxe2x88x92, CF3(CF2)3SO3xe2x88x92, [CF3SO2]2Nxe2x88x92, or a metal inorganic anion. Most preferably, the anionic species Bxe2x88x92 will be selected from BF4xe2x88x92 and PF6xe2x88x92.
In another embodiment, a basic ionic liquid is used as both the reaction medium and catalyst for producing aldol condensation products. The cationic species A+ of the basic ionic liquid is selected from those enumerated above for the cationic species of the neutral ionic liquids. However, the anionic species Bxe2x88x92 of the basic ionic liquid is a hydroxyl group. This basic ionic liquid is typically formed by reacting an ionic liquid precursor with either an alkali metal hydroxide or alkali earth metal hydroxide in a tetrahydrofuran medium with the loss of a salt, as is known by one skilled in the art. The most preferred anionic species are those prepared from potassium hydroxide or sodium hydroxide. For instance, an imidazolium chloride may be reacted with potassium hydroxide to form the basic ionic liquid imidazolium hydroxide with the loss of a potassium chloride salt. An example of the formation of a basic ionic liquid is shown in Examples 7 and 8 herein.
Any aldehyde may be used as the aldehyde starting material in the present case. The only limitation is that in an Aldol I reaction, two molecules of the same aldehyde starting material react to form aldol condensation products. Alternatively, an Aldol II reaction involves reacting two different aldehyde starting materials to produce the condensation products. The preferred aldehyde starting materials utilized in forming the aldol condensation products are one or more aldehydes having the formula RCHO, wherein R is a hydrogen atom or a straight-chain, branched or cyclic aliphatic group having from 1 to 10 carbon atoms, preferably from 1 to 6 carbon atoms, and most preferably from 1 to 4 carbon atoms.
In a further embodiment, a commercially important application of cross-aldol condensation (Aldol II) is the reaction of formaldehyde with a second aldehyde starting to form a neopolyol. In practice, several intermediate aldol addition steps involving formaldehyde and a final crossed Cannizzaro step take place before producing the neopolyol product. The most preferred second aldehyde starting materials are acetaldehyde, propionaldehyde, n-butyraldehyde and isobutyraldehyde, which, when reacted with formaldehyde, produce the respective neopolyol products pentaerythritol, trimethylol ethane, trimethylol propane and neopentyl glycol.
The above-referenced reactions for forming aldol condensation products may be generally carried out at a pressure of from about 1 atm (atmospheric pressure) to about 1000 atm (elevated pressure). The reaction can be carried out over a wide range of temperatures and is not particularly limited. Usually the reaction temperature is within the range of from about xe2x88x9220xc2x0 C. to 300xc2x0 C., more typically within the range of from 50xc2x0 C. to 250xc2x0 C., such as from 60xc2x0 C. to 150xc2x0 C. Preferably, the temperature ranges from 70xc2x0 C. to 100xc2x0 C. Most preferably, the temperature is from 80xc2x0 C. to 90xc2x0 C.
The aldol condensation reactions of the instant case may run for approximately from about 1 to 10 hours, preferably from about 2 to 5 hours, and most preferably for about 3 hours.
In the present invention, the ionic liquid phase can be recycled by way of methods known in the art and applied as reaction medium to form additional aldol condensation products. The ionic liquid medium may also be recycled for use in other reactions.